| Publication Abstract Display | | Type: Published Abstract | | Title: Seminal Ccytokine/chemokine network and HIV transmission in men who have sex with men. | | Authors: Vanpouille C, Lisco A, Margolis L, Layman L, Hoenigl M, Gianella S | | Year: | | Publication: CROI 2018 | | Volume: Issue: Pages: | | Abstract:The cytokine/chemokine network in genital secretion reflects the functional status of immune cells in the genital tract, where the key events related to sexual transmission occur. Here, we describe differences in cytokine/chemokine levels in semen between HIV-infected men who did transmit and did not transmit HIV to their male sexual partner.
Participants were men with primary HIV infection and their recent male sexual partners (HIV-positive or negative). HIV transmission among sero-concordant partnerships was defined as phylogenetic linkage (≤1.5% genetic distance in pol), and the HIV-positive partner with the earlier estimated date of infection (EDI) was considered the source. Among sero-discordant couples, the HIV-positive partner was considered the (potential) source. All analyses were restricted to source partners. Sources with sero-discordant partners were classified as non-transmitters (n=23), and those with sero-concordant phylogenetically-linked partners were considered transmitters (n=21). For each source partner (transmitter or non-transmitter), semen was collected and a panel of 34 cytokine/chemokines were measured by Luminex. Principal-components and clustering methods were used to select cytokine/chemokines with the strongest association with transmission, which were included in a multiple logistic regression model in the presence of the following covariates from the source partner: ART status, EDI, age, race/ethnicity, CD4+ and CD8+ cells, HIV RNA levels in blood and semen, presence of seminal HSV-2, EBV or CMV DNA.
At the univariate level, participants classified as transmitters had significantly higher levels of IL-13, lower levels of M-CSF, INF-, IL-17, TGF- and Eotaxin compared to non-transmitters (Table 1). Individuals classified as transmitters were also more likely to be ART naïve, HIV-infected for >1 year, have lower CD4+ cells, detectable seminal HIV RNA and EBV DNA. In multivariable model, higher IL-13, lower Eotaxin and detectable HIV RNA in semen remained significantly associated with presence of HIV transmission within the observed partnership.
While detectable HIV RNA in semen was the strongest predictor of HIV transmission, altered cytokine/chemokine network might play a role in HIV transmission. For example, the observed association between higher IL-13 and HIV transmission is consistent with previous vaccine studies reporting stronger anti-HIV response when inhibitors of IL-13 were used and should be further investigated. |
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